Neanderthals are the closest relatives of modern humans. Therefore, comparing them can provide fascinating insights into what makes modern humans unique, for example regarding brain development. The neocortex, the largest part of the outer layer of the brain, is unique to mammals and is critical to many cognitive abilities. It expanded dramatically during human evolution in the species ancestral to both Neanderthals and modern humans, resulting in both Neanderthals and modern humans having the same brain size. However, almost nothing is known about the extent to which the brains of modern humans and Neanderthals may have differed in their development and function.
Researchers at the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden and the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig have now discovered that neural stem cells—the cells from which neurons in the developing cerebral cortex—spend more time to prepare their chromosomes to divide in modern humans than in Neanderthals. This results in fewer errors in the distribution of chromosomes in the daughter cells of modern humans than in Neanderthals or chimpanzees, and may have implications for brain development and function. This study shows cellular differences in brain development between modern humans and Neanderthals.
After the ancestors of modern humans separated from the ancestors of Neanderthals and Denisovans, their Asian relatives, about a hundred amino acids, the building blocks of proteins in cells and tissues, changed in modern humans and spread to almost all modern humans. The biological significance of these changes is largely unknown. However, six of these amino acid changes occurred in three proteins that play a key role in the distribution of chromosomes, carriers of genetic information, into the two daughter cells during cell division.
The impact of modern human variants on brain development
To investigate the significance of these six changes for the development of the cerebral cortex, the scientists first introduced modern human variants to mice. Mice are identical to Neanderthals at these six amino acid positions, so these changes made them a model for the development of the modern human brain. Felipe Mora-Bermúdez, lead author of the study, describes the discovery: “We found that three modern human amino acids in two proteins cause a longer metaphase, the phase when chromosomes prepare for cell division, and this leads to less error when the chromosomes are distributed by daughter cells of neural stem cells, as in modern humans.’ To test whether the Neanderthal set of amino acids had the opposite effect, the researchers injected the ancestral amino acids into human brain organoids—miniature organ-like structures that can be grown from human stem cells in a cell culture lab. Mimic Aspects of Early Human Brain Development. “In this case, the metaphase was shorter and we found more errors in chromosome distribution.” According to Moreau-Bermúdez, this shows that these three modern human amino acid changes in proteins known as KIF18a and KNL1 are responsible for the fewer errors in chromosome distribution seen in modern humans compared to the Neanderthal and chimpanzee models. He adds that “errors in the number of chromosomes are generally not a good idea for cells, as can be seen in disorders such as trisomy and cancer.”
“Our study suggests that some aspects of the evolution and functioning of the modern human brain may be independent of brain size, as Neanderthals and modern humans have the same brain size. The results also suggest that Neanderthal brain functions may have been more affected by chromosomal errors than modern humans,” concludes Wieland Huttner, who led the study. Svante Pääbo, who also led the study, adds that “future research is needed to to investigate whether the reduction in error rates affects traits related to brain function in modern humans.”
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